This Center grant requests funding for seven Core facilities to support a broadly-based research program in the study of mental retardation and developmental disabilities. The seven Core facilities are: Administrative, Multimedia, Image Graphics/Confocal, Cellular Neuroscience, Gene Manipulation, Molecular Genetics, and Cell Sorter. The Cores, which are derived from the previous 10 Core facilities of the Center, have undergone major development and support the research of 49 investigators who receive approximately $14,700,000 in external funding, approximately $13,000,000 of which is from the NIH. The research is in two programmatic areas, i.e., Genetics and Neuroscience. In Genetics, directed by Dr. Louis Kunkel, there are five major research efforts: molecular genetics of neuromuscular disease, genetic imprinting in Angelman and Prader-Willi syndromes, molecular diagnosis, dystrophin-related proteins in brain, and somatic cell genetics. In Neuroscience, there are three major programs, i.e., Basic Neuroscience, directed by the newly- recruited Associate Director of the Center, Dr. Michael Greenberg; Clinical Neuroscience/Behavior, directed by the Center Director; and Developmental Biology, directed by Dr. Merton Bernfield. The Basic Neuroscience Program consists of 23 funded investigators whose research efforts span a broad spectrum of interdigitated research in molecular, cellular, ultrastructural, and systems neuroscience, with a strong overall emphasis on development. A research project in Basic Neuroscience, proposed in this grant as a "New Program", addresses "Mechanisms of Glutamate- Mediated Immediate Early Gene Expression" (Stephen Finkbeiner, M.D., Ph.D). A second major program in Neuroscience, i.e., Clinical Neuroscience/Behavior, directed by the Center Director, has undergone marked development in terms of investigators and scope of research. The research areas include: ischemic neonatal brain injury, neurocardiology, behavioral and neurophysiological development, developmental psychology and learning disturbances, development of human visual function, HIV and the developing nervous system, and effects of endogenous and exogenous toxins on brain development. These areas of clinical research interdigitate with the basic research in the MRRC. A third exciting program in Neuroscience, i.e., Developmental Biology, directed by Dr. Merton Bernfield, addresses fundamental mechanisms of cellular organization during embryonic development, particularly the interaction of cell surface molecules with the extracellular matrix. The multidisciplinary approaches to the research of this MRRC include the various basic science disciplines within Genetics and Neuroscience, and the clinical science fields of Neurology, Pediatrics, Neonatology, Infectious Disease, Endocrinology, Metabolism, Genetics, Cardiology, Neurosurgery, Neuropathology, Ophthalmology, Psychiatry, and Psychology. The basic science programs are housed in over 50,000 sq. ft. of the Enders Pediatric Research Building. The clinical research programs are centered in the adjacent Children's Hospital.